Aim: The aim of this study was to evaluate differences in the inflammatory profile of young (≤40 years) systemically healthy periodontal patients comparing chronic (CP) versus aggressive periodontitis (AP) in terms of cytokines, chemokines and C-reactive protein levels. Methods: Systemically healthy subjects affected by severe CP or AP were enrolled in this study. Differential diagnosis was performed according to the criteria suggested by the American Academy of Periodontology. Blood samples for the evaluation of high sensitivity C-reactive protein levels, cytokine levels (IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12, interferon-γ, interferon-γ-inducible protein 10, tumour necrosis factor α) and chemokine levels (IL-8, vascular endothelial growth factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α and macrophage inflammatory protein 1β) were obtained from all patients. Results: A total of 45 systemically healthy patients with severe periodontitis were consecutively selected, 21 with CP (mean age 36.8 ± 3.5; mean clinical attachment level [CAL] 4.72 ± 0.69) and 24 with AP (mean age 35.9 ± 3.8; mean CAL 4.68 ± 0.75). No statistically significant difference between the two groups was detected for periodontal variables and for all the investigated inflammatory markers. Conclusions: The inflammatory profile of severe periodontitis in young patients (≤40 years) may be similar for chronic and aggressive types. Differential diagnosis between CP and AP may not be able to detect a different systemic inflammatory profile in young adults.